Application of Peak Glucose Range and Diabetes Status in Mortality Risk Stratification in Critically Ill Patients with Sepsis

The effects of diabetes and glucose on the outcomes of patients with sepsis are somewhat conflicting. This retrospective study enrolled 1214 consecutive patients with sepsis, including a subpopulation of 148 patients with immune profiles. The septic patients were stratified according to their Diabetes mellitus (DM) status or peak glucose level (three-group tool; P1: ≤140 mg/dL, P2: 141–220 mg/dL, P3: >220 mg/dL) on day 1. Although the DM group had a lower hazard ratio (HR) for 90-day mortality compared to non-DM patients, the adjusted HRs were insignificant. The modified sequential organ failure assessment-glucose (mSOFA-g) score can predict 90-day survival in patients with and without diabetes (β = 1.098, p < 0.001; β = 1.202, p < 0.001). The goodness of fit of the mSOFA-g score was 5% higher than the SOFA score of the subgroup without diabetes. The SOFA score and human leukocyte antigen-D-related (HLA-DR) expression were comparable between the groups. The P3 group had lower HLA-DR expression on days 1 and 3 and a higher 90-day mortality. The three-group tool was useful for predicting 90-day mortality in patients with separate Kaplan-Meier survival curves and mortality HRs in the construction and validation cohorts. The peak glucose level, instead of diabetes status, can be used as an easy adjunctive tool for mortality risk stratification in critically ill septic patients.

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Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

Annals of Intensive Care ◽

10.1186/s13613-021-00896-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Clémence Marais ◽

Caroline Claude ◽

Nada Semaan ◽

Ramy Charbel ◽

Simon Barreault ◽

...

Keyword(s):

Critically Ill ◽

Host Response ◽

Secondary Infection ◽

Myeloid Cells ◽

Suppressor Cells ◽

Human Leukocyte ◽

Myeloid Derived Suppressor Cells ◽

Phenotypic Characteristics ◽

Leukocyte Antigen ◽

Hla Dr

Abstract Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

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Validation of a 12-mRNA Score for Mortality Risk Stratification in Critically Ill Patients

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2388 ◽

2019 ◽

Author(s):

A. Moore ◽

J. Roque ◽

B.D. Shaller ◽

T. Asuni ◽

J.E. Levitt ◽

...

Keyword(s):

Risk Stratification ◽

Critically Ill ◽

Mortality Risk ◽

Critically Ill Patients

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ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

10.1101/2021.01.20.21250182 ◽

2021 ◽

Author(s):

Eleni Karakike ◽

George N. Dalekos ◽

Ioannis Koutsodimitropoulos ◽

Maria Saridaki ◽

Chryssa Pourzitaki ◽

...

Keyword(s):

Critically Ill ◽

Sofa Score ◽

Mononuclear Cells ◽

Prospective Trial ◽

Study Endpoint ◽

Primary Study ◽

Open Label ◽

Urokinase Plasminogen Activator Receptor ◽

Hla Dr ◽

Secondary Infections

ABSTRACTRationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.Trial RegistrationClinicalTrials.gov, NCT04339712

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Insufficient Nutrition and Mortality Risk in Septic Patients Admitted to ICU with a Focus on Immune Dysfunction

Nutrients ◽

10.3390/nu11020367 ◽

2019 ◽

Vol 11 (2) ◽

pp. 367 ◽

Cited By ~ 4

Author(s):

Kai-Yin Hung ◽

Yu-Mu Chen ◽

Chin-Chou Wang ◽

Yi-Hsi Wang ◽

Chiung-Yu Lin ◽

...

Keyword(s):

Synergistic Effect ◽

Critically Ill ◽

Prospective Observational Study ◽

Caloric Intake ◽

Human Leukocyte ◽

Immune Dysfunction ◽

Leukocyte Antigen ◽

Hla Dr ◽

Failure Assessment ◽

Baseline Characteristics

Immune dysfunction is seen both in sepsis patients and in those with malnutrition. This study aimed to determine whether insufficient nutrition and immune dysfunction have a synergistic effect on mortality in critically ill septic patients. We conducted a prospective observational study from adult sepsis patients admitted to intensive care units (ICUs) between August 2013 and June 2016. Baseline characteristics including age, gender, body mass index, NUTRIC, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were recorded. Immune dysfunction, defined by human leukocyte antigen DR (HLA-DR) expression, was tested at days 1, 3, and 7 of ICU admission. The study included 151 patients with sepsis who were admitted to the ICU. The 28-day survivors had higher day 7 caloric intakes (89% vs 73%, p = 0.042) and higher day 1-HLA-DR expression (88.4 vs. 79.1, p = 0.045). The cut-off points of day 7 caloric intake and day 1-HLA-DR determined by operating characteristic curves were 65.1% and 87.2%, respectively. Immune dysfunction was defined as patients with day 1-HLA-DR < 87.2%. Insufficient nutrition had no influence on survival outcomes in patients with immune dysfunction. However, patients with insufficient nutrition had poor prognosis when they were immune competent. Insufficient nutrition and immune dysfunction did not have a synergistic effect on mortality in critically ill septic patients.

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Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Diagnostics ◽

10.3390/diagnostics11071249 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1249

Author(s):

Chrysi Keskinidou ◽

Alice G. Vassiliou ◽

Alexandros Zacharis ◽

Edison Jahaj ◽

Parisis Gallos ◽

...

Keyword(s):

Critically Ill ◽

Mortality Risk ◽

Roc Curves ◽

Mortality Prediction ◽

Prognostic Biomarkers ◽

Inflammatory Biomarkers ◽

Rank Test ◽

Icu Mortality ◽

Icu Admission ◽

Kaplan Meier

Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

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ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

Journal of Innate Immunity ◽

10.1159/000519090 ◽

2021 ◽

pp. 1-11

Author(s):

Eleni Karakike ◽

George N. Dalekos ◽

Ioannis Koutsodimitropoulos ◽

Maria Saridaki ◽

Chryssa Pourzitaki ◽

...

Keyword(s):

Sofa Score ◽

Mononuclear Cells ◽

Prospective Trial ◽

Human Leukocyte ◽

Standard Of Care ◽

Study Endpoint ◽

Primary Study ◽

Open Label ◽

Urokinase Plasminogen Activator Receptor ◽

Hla Dr

Background: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. Methods: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. Results: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. Conclusion: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.

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Glycemic Variability Is Associated With All-Cause Mortality In COVID-19 Patients With ARDSFindings From The COVAS Cohort

10.21203/rs.3.rs-1111538/v1 ◽

2022 ◽

Author(s):

Bojan Hartmann ◽

Marlo Verket ◽

Paul Balfanz ◽

Niels-Ulrik Hartmann ◽

Malte Jacobsen ◽

...

Keyword(s):

Goodness Of Fit ◽

Distress Syndrome ◽

Glycemic Variability ◽

University Hospital ◽

Cox Models ◽

Kaplan Meier ◽

Diabetes Status ◽

Significant Difference ◽

All Cause Mortality ◽

Proportional Increase

Abstract There is high mortality among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease 19 (COVID-19). Important factors for COVID-19 mortality are diabetes status and elevated fasting plasma glucose (FPG). However, the effect of glycemic variability on survival has not been explored in patients with COVID-19 and ARDS. This single-centre cohort-study compared several metrics of daily glycemic variability (DGV) for goodness-of-fit in patients requiring mechanical ventilation due to COVID-19 ARDS in the ICU at University Hospital Aachen, Germany. 106 patients had moderate to severe ARDS (P/F ratio median [IQR]: 112 [87-148] mmHg). Continuous HRs showed a proportional increase in mortality risk with DGV. Multivariable unadjusted and adjusted Cox-models showed a statistically significant difference in mortality for DGV (HR: 1.02, (P)<0.001, LR(P)<0.001; HR: 1.016, (P)=0.001, LR(P)<0.001, respectively). Kaplan-Meier estimators yielded a shorter median survival (25 vs. 87 days) and higher likelihood of death (75% vs. 31%) in patients with DGV ≥ 25.5mg/dl (P<0.0001). High glycemic variability during ICU admission is associated with significant increase in all-cause mortality for patients admitted with COVID-19 ARDS to the ICU. This effect persisted even after adjustment for clinically predetermined confounders, including diabetes, procalcitonin and FPG levels at baseline.

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Cystatin C predicts long term mortality better than creatinine in a nationwide study of intensive care patients

Scientific Reports ◽

10.1038/s41598-021-85370-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Johanna Helmersson-Karlqvist ◽

Miklos Lipcsey ◽

Johan Ärnlöv ◽

Max Bell ◽

Bo Ravn ◽

...

Keyword(s):

Intensive Care ◽

Critically Ill ◽

Risk Prediction ◽

Cystatin C ◽

Mortality Risk ◽

Critically Ill Patients ◽

Cox Regression ◽

Sample Tube ◽

Long Term Mortality

AbstractDecreased glomerular filtration rate (GFR) is linked to poor survival. The predictive value of creatinine estimated GFR (eGFR) and cystatin C eGFR in critically ill patients may differ substantially, but has been less studied. This study compares long-term mortality risk prediction by eGFR using a creatinine equation (CKD-EPI), a cystatin C equation (CAPA) and a combined creatinine/cystatin C equation (CKD-EPI), in 22,488 patients treated in intensive care at three University Hospitals in Sweden, between 2004 and 2015. Patients were analysed for both creatinine and cystatin C on the same blood sample tube at admission, using accredited laboratory methods. During follow-up (median 5.1 years) 8401 (37%) patients died. Reduced eGFR was significantly associated with death by all eGFR-equations in Cox regression models. However, patients reclassified to a lower GFR-category by using the cystatin C-based equation, as compared to the creatinine-based equation, had significantly higher mortality risk compared to the referent patients not reclassified. The cystatin C equation increased C-statistics for death prediction (p < 0.001 vs. creatinine, p = 0.013 vs. combined equation). In conclusion, this data favours the sole cystatin C equation rather than the creatinine or combined equations when estimating GFR for risk prediction purposes in critically ill patients.

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Risk assessment in precapillary pulmonary hypertension: a comparative analysis

Respiratory Research ◽

10.1186/s12931-021-01624-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thomas Sonnweber ◽

Eva-Maria Schneider ◽

Manfred Nairz ◽

Igor Theurl ◽

Günter Weiss ◽

...

Keyword(s):

Risk Assessment ◽

Pulmonary Hypertension ◽

High Risk ◽

Risk Stratification ◽

Risk Prediction ◽

Mortality Risk ◽

Assessment Tool ◽

Risk Models ◽

Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

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Were VCF patients at higher risk of mortality following the 2009 publication of the vertebroplasty “sham” trials?

Osteoporosis International ◽

10.1007/s00198-017-4281-z ◽

2017 ◽

Vol 29 (2) ◽

pp. 375-383 ◽

Cited By ~ 25

Author(s):

K. L. Ong ◽

D. P. Beall ◽

M. Frohbergh ◽

E. Lau ◽

J. A. Hirsch

Keyword(s):

Mortality Risk ◽

Cox Regression ◽

Compression Fracture ◽

Balloon Kyphoplasty ◽

Data Set ◽

Mortality Risks ◽

Medicare Data ◽

Kaplan Meier ◽

Risk Of Mortality ◽

Insight Into

Abstract Summary The 5-year period following 2009 saw a steep reduction in vertebral augmentation volume and was associated with elevated mortality risk in vertebral compression fracture (VCF) patients. The risk of mortality following a VCF diagnosis was 85.1% at 10 years and was found to be lower for balloon kyphoplasty (BKP) and vertebroplasty (VP) patients. Introduction BKP and VP are associated with lower mortality risks than non-surgical management (NSM) of VCF. VP versus sham trials published in 2009 sparked controversy over its effectiveness, leading to diminished referral volumes. We hypothesized that lower BKP/VP utilization would lead to a greater mortality risk for VCF patients. Methods BKP/VP utilization was evaluated for VCF patients in the 100% US Medicare data set (2005–2014). Survival and morbidity were analyzed by the Kaplan-Meier method and compared between NSM, BKP, and VP using Cox regression with adjustment by propensity score and various factors. Results The cohort included 261,756 BKP (12.6%) and 117,232 VP (5.6%) patients, comprising 20% of the VCF patient population in 2005, peaking at 24% in 2007–2008, and declining to 14% in 2014. The propensity-adjusted mortality risk for VCF patients was 4% (95% CI, 3–4%; p < 0.001) greater in 2010–2014 versus 2005–2009. The 10-year risk of mortality for the overall cohort was 85.1%. BKP and VP cohorts had a 19% (95% CI, 19–19%; p < 0.001) and 7% (95% CI, 7–8%; p < 0.001) lower propensity-adjusted 10-year mortality risk than the NSM cohort, respectively. The BKP cohort had a 13% (95% CI, 12–13%; p < 0.001) lower propensity-adjusted 10-year mortality risk than the VP cohort. Conclusions Changes in treatment patterns following the 2009 VP publications led to fewer augmentation procedures. In turn, the 5-year period following 2009 was associated with elevated mortality risk in VCF patients. This provides insight into the implications of treatment pattern changes and associated mortality risks.

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